Genetic Evidence of a Recent Decline and Crossbreed Distribution of TRPV4 c.1024G>T Variant in Domestic Cats.

Abstract

The folded ear phenotype of Scottish Fold cats is associated with an autosomal dominant TRPV4 variant (c.1024G>T) linked to osteochondrodysplasia. Although genetic testing has been implemented to guide breeding, empirical evidence of its impact on allele frequency remains limited, and crossbreed investigations are lacking. Here, we evaluated longitudinal changes in TRPV4 c.1024G>T allele frequencies in Scottish Folds and surveyed the variant in 8610 cats from 14 breeds in Japan. Overall, between 2017 and 2024, the proportion of homozygous cats significantly declined (from 14.2% to 1.9%, p&#x2009;<&#x2009;0.001), whereas the frequency of heterozygous cats remained stable (39.3% vs. 51.5%, p&#x2009;>&#x2009;0.74). The variant was identified primarily in Scottish Folds but was also detected in American Curls, Norwegian Forest Cats, Munchkins, and Minuets. Taken together, our results highlight that integrating TRPV4 c.1024G>T genotyping into breeding programs can effectively reduce the prevalence of this hereditary disorder, and they warrant the expansion of genetic testing to additional breeds.